The goal of this study was to establish a computational fluid dynamics model to investigate the effect of cyclic motion (i.e., bending and stretching) on coronary blood flow. The three-dimensional (3D) geometry of a 50-mm section of the left anterior descending artery (normal or with a 60% stenosis) was constructed based on anatomical studies. To describe the bending motion of the blood vessel wall, arbitrary Lagrangian–Eularian methods were used. To simulate artery bending and blood pressure change induced stretching, the arterial wall was modeled as an anisotropic nonlinear elastic solid using the five-parameter Mooney–Rivlin hyperelastic model. Employing a laminar model, the flow field was solved using the continuity equations and Navier–Stokes equations. Blood was modeled as an incompressible Newtonian fluid. A fluid–structure interaction approach was used to couple the fluid domain and the solid domain iteratively, allowing force and total mesh displacement to be transferred between the two domains. The results demonstrated that even though the bending motion of the coronary artery could significantly affect blood cell trajectory, it had little effect on flow parameters, i.e., blood flow velocity, blood shear stress, and wall shear stress. The shape of the stenosis (asymmetric or symmetric) hardly affected flow parameters either. However, wall normal stresses (axial, circumferential, and radial stress) can be greatly affected by the blood vessel wall motion. The axial wall stress was significantly higher than the circumferential and radial stresses, as well as wall shear stress. Therefore, investigation on effects of wall stress on blood vessel wall cellular functions may help us better understand the mechanism of mechanical stress induced cardiovascular disease.